Aggression, childhood adversity, and the response to stress are all critical factors contributing to risk for suicidal behavior. However, the relationships among these variables and their relative contribution to suicidal behavior are not well-understood, in part, due to limitations in measures. Conceptually, there may be multiple dimensions or subtypes of each that contribute to suicide risk in different ways The goal of this project is characterize the extent and nature of aggressive behavior exhibited by participants, relate it to detailed assessments of types of childhood adversity as well as to situational, psychobiological responses to stress, and ultimately relate all of these to suicidal behavior in suicide attempters and non-attempters with major depressive disorder, high-risk offspring of suicidal individuals, and healthy volunteers. Aggressiveness will be assessed via interview, self report and a behavioral measure (Point Subtraction Aggression Paradigm) to characterize the reactive vs. proactive nature of the behavior. While Reactive Aggression - characterized by acute responses to situational provocation and emotional volatility - is thought to underlie a substantial portion of suicidal behavior, Proactive Aggression - more deliberate behaviors with less overt emotional reactivity - has been less systematically studied, but has also been related to suicidal behavior Childhood adversity will be assessed via the Childhood Trauma Questionnaire, a measure that distinguishes among physical abuse, sexual abuse, and emotional abuse/neglect. Our preliminary data indicate that the effect of past abuse on suicidal behavior is mediated by aggression. Stress response will be assessed via behavioral and Cortisol responses to the Trier Social Stress Test. Our preliminary data indicate that heightened Cortisol response to this stressor is evident in those with high impulsive aggression, a group that does not encompass all suicide attempters. Thus, there is a subtype of attempter who appears more sensitive to these situational stressors, but another subtype - currently poorly characterized - that does not. Ultimately, this project will make a major contribution toward characterizing alternative pathways to suicidal behavior, with potentially different underlying neurobiological mechanisms. In conjunction with data from PET receptor studies of the serotonin transporter (Project 3) and functional magnetic resonance imaging studies of emotional regulation (Project 4), these studies will identify relationships among these biological and behavioral measures that can provide targets for intervention more closely tailored to individual needs.